Hundreds of thousands of women in the United States suffer from vulvodynia a chronic burning vulvar pain of unknown cause. Millions of health care dollars are spent annually for this disorder in the United States alone, not only on management, but also on the large proportion of cases that are misdiagnosed and inadequately treated. This pain, associated with allodynia and hyperpathia, has a strong genetic predelection, with African- American women rarely being affected. The broad, long-term objectives of this proposal are to assess the differences in specific neuroimmunological characteristics between women with vulvodynia and asymptomatic controls. The specific aims include: evaluation of l) the individual cytokine/neurokine production response to stimulation of peripheral blood; 2) local changes in nerve fiber, mast cell, Substance P and serotonin density in vulvar tissue; 3) the interactions of the systemic and local immunologic systems assessed in l) and 2); and 4) the multivariable assessment of these laboratory factors with historical risk factors for vulvodynia to explore potential pathophysiologic mechanisms accounting for the historical risk factors identified. The research design involves a case-control evaluation of 100 women with vulvodynia, 100 controls matched for ethnicity, and 100 African-American control women, using questionnaires, physical examinations, clinical laboratory data, cytokine/neurokine levels in stimulated peripheral blood, and neuroimmunohistological assessment of vulvar biopsy specimens for nerve fiber density, mast cells, Substance P and serotonin. Results from this study will lead to improved understanding of neuroimmunologic alterations in women with vulvodynia which will direct future therapeutic strategies for this disorder.